It is well known that sensorimotor functions, including strength and endurance, are affected by the aging process. Changes in muscle function with age (sarcopenia) are associated with reductions in muscle mass and cross sectional area, reductions in the number of motor units and transformations or selective loss of specific muscle fiber types. Sarcopenia is not limited to muscles within the extremities; age-related decrements in critical cranial functions, such as swallowing, have also been reported. The tongue has a vital role in swallowing and poor lingual function is associated with swallowing impairment. Tongue muscle atrophy and/or weakness may contribute to this phenomenon. However, it may be possible to intervene in the aging process because skeletal muscles can adapt at multiple levels of structure and function to changing demands, levels of activity and hormonal conditions. Recent studies suggest that targeted tongue exercise and/or neuromuscular electrical stimulation (NMES) is associated with alterations in tongue strength, physiology and phenotype. However, feasible and optimal treatment doses have not been established and it has not been determined if targeted NMES alone or in combination with tongue exercise is required for benefit to the behavioral end product - the swallow. Our hypothesis is that age-related decline in swallowing function is largely due to alterations in tongue muscle structure, function, and neuromuscular integrity. Further, we hypothesize that targeted NMES treatment, behavioral tongue exercise, or a combination of exercise and NMES will result in phenotypic changes in 3 extrinsic tongue muscles of old and middle-aged rats that will facilitate improvements in measures in deglutition. We will test this hypothesis in a rat model by comparing physiological, behavioral, biochemical, molecular and morphological parameters in rats of different ages that have undergone 8 weeks of bilateral stimulation of the hypoglossal nerves to model NMES, tongue exercise, or NMES plus tongue exercise versus sham- treated and no-treatment controls. The proposed research has three specific aims: (1) To determine the manner in which NMES treatment dose affects morphological, biochemical, molecular, physiological changes in aged tongue muscles; (2) To determine if targeted treatment with NMES is sufficient to optimize changes in aged tongue muscle phenotype and physiology or if behavioral tongue exercise in addition to NMES is required for such optimization, and (3) To discover how age and treatment variables affect measures of deglutition in an animal model. This work is translational, innovative and important in discovering a neuromuscular basis for the putative benefits of NMES and/or tongue exercise in the prevention and treatment of age-related swallowing impairment. PUBLIC HEALTH RELEVANCE: Aging is associated with disruptions in the ability to swallow safely. The tongue has an important role in swallowing. This work will examine, using a rat model, whether neuromuscular electrical stimulation and exercise are effective in modifying tongue muscle structure, biochemical composition, mitochondrial DNA, and physiology. We will determine if changes in these variables are related to changes in swallowing behaviors in aged rats.